tbuckley/cabot-search huggingface dataset:
A bioinspired and high-strengthed hydrogel for regeneration of perforated temporomandibular joint disc: Construction and pleiotropic immunomodulatory effects
Authors: Xiao Xu, Baiyan Sui, Xin Liu, Jiao Sun
Journal: Bioactive Materials (2022)

Due to the lack of an ideal material for TMJ (temporomandibular joint) disc perforation and local inflammation interfering with tissue regeneration, a functional TGI/HA-CS (tilapia type I gelatin/hyaluronic acid-chondroitin sulfate) double network hydrogel was constructed in this paper. It was not only multiply bionic in its composition, structure and mechanical strength, but also endowed with the ability to immunomodulate microenvironment and simultaneously induce in situ repair of defected TMJ discs. On the one hand, it inhibited inflammatory effects of inflammasome in macrophages, reduced the extracellular matrix (ECM)-degrading enzymes secreted by chondrocytes, reversed the local inflammatory state, promoted the proliferation of TMJ disc cells and induced fibrochondrogenic differentiation of synovium-derived mesenchymal stem cells (SMSCs). On the other hand, it gave an impetus to repairing a relatively-large (6 mm-sized) defect in mini pigs' TMJ discs in a rapid and high-quality manner, which suggested a promising clinical application.
Progress in non-viral localized delivery of siRNA therapeutics for pulmonary diseases
Authors: Jingjing Gao, Ziting Xia, Dilrasbonu Vohidova, John Joseph, James N. Luo, Nitin Joshi
Journal: Acta Pharmaceutica Sinica B (2022)

Emerging therapies based on localized delivery of siRNA to lungs have opened up exciting possibilities for treatment of different lung diseases. Localized delivery of siRNA to lungs has shown to result in severalfold higher lung accumulation than systemic route, while minimizing non-specific distribution in other organs. However, to date, only 2 clinical trials have explored localized delivery of siRNA for pulmonary diseases. Here we systematically reviewed recent advances in the field of pulmonary delivery of siRNA using non-viral approaches. We firstly introduce the routes of local administration and analyze the anatomical and physiological barriers towards effective local delivery of siRNA in lungs. We then discuss current progress in pulmonary delivery of siRNA for respiratory tract infections, chronic obstructive pulmonary diseases, acute lung injury, and lung cancer, list outstanding questions, and highlight directions for future research. We expect this review to provide a comprehensive understanding of current advances in pulmonary delivery of siRNA.
Self-therapeutic metal-based nanoparticles for treating inflammatory diseases
Authors: Ruifang Han, Yu Xiao, Qianqian Bai, Chung Hang Jonathan Choi
Journal: Acta Pharmaceutica Sinica B (2022)

Inflammatory diseases are key contributors to high mortality globally and adversely affect the quality of life. Current treatments include corticosteroids or nonsteroidal anti-inflammatories that may cause systemic toxicity and biologics that may increase the risk of infection. Composite nanoparticles that bear not only the drug payload but also targeting ligands for delivery to inflammation sites at lowered systemic toxicity are established in the nanomedicine field, but their relatively large size often leads to systemic clearance. Metal-based nanoparticles with intrinsic anti-inflammatory properties represent attractive alternatives. They are not only designed to be compact for crossing biological barriers (with the nanoparticle serving as a dual carrier and drug), but also support label-free tracking of their interactions with cells. The review commences with an outline of the common inflammatory diseases, inflammatory pathways involved, and conventional drug-loaded nanoparticles for anti-inflammation. Next, the review features the emerging applications of self-therapeutic metal-based nanoparticles (e.g., gold, coper oxide, platinum, ceria, and zinc oxide) for managing inflammatory diseases in animals over the past three years, focusing on therapeutic outcomes and anti-inflammatory mechanisms. The review concludes with an outlook on the biodistribution, long-term toxicity, and clinical translation of self-therapeutic metal-based nanoparticles.
Safety and efficacy of liraglutide versus colesevelam for the treatment of bile acid diarrhoea: a randomised, double-blind, active-comparator, non-inferiority clinical trial
Authors: Martin L Kårhus, Andreas Brønden, Julie L Forman, Anne Haaber, Elisabeth Knudsen, Ebbe Langholz, Lars O Dragsted, Svend H Hansen, Martin Krakauer, Tina Vilsbøll, David P Sonne, Filip K Knop
Journal: The Lancet. Gastroenterology & hepatology (2022)
Systemic therapy and perioperative management improve the prognosis of pancreatic ductal adenocarcinoma: A retrospective cohort study of 2000 consecutive cases
Authors: Guoxiao Zhang, Bo Li, Xiaoyi Yin, Suizhi Gao, Shuo Shen, Huan Wang, Xiaohan Shi, Wuchao Liu, Kailian Zheng, Wei Jing, Yijie Zhang, Tianlin He, Gang Li, Xiangui Hu, Shiwei Guo, Gang Jin
Journal: International Journal of Surgery (2022)
Effectiveness of a pay-it-forward intervention compared with user-paid vaccination to improve influenza vaccine uptake and community engagement among children and older adults in China: a quasi-experimental pragmatic trial
Authors: Dan Wu, Chenqi Jin, Khaoula Bessame, Fanny Fong-Yi Tang, Jason J Ong, Zaisheng Wang, Yewei Xie, Mark Jit, Heidi J Larson, Tracey Chantler, Leesa Lin, Wenfeng Gong, Fan Yang, Fengshi Jing, Shufang Wei, Weibin Cheng, Yi Zhou, Nina Ren, Shuhao Qiu, Jianmin Bao, Liufen Wen, Qinlu Yang, Junzhang Tian, Weiming Tang, Joseph D Tucker
Journal: The Lancet Infectious Diseases (2022)

China has low seasonal influenza vaccination rates among priority populations. In this study, we aimed to evaluate a pay-it-forward strategy to increase influenza vaccine uptake in rural, suburban, and urban settings in China.
ROS Turn Nanoparticle Fluorescence on for Imaging <i>Staphylococcus aureus</i> Infection In Vivo (Adv. Healthcare Mater. 14/2022)
Authors: Lingling Xu, Wenjun Zhan, Yu Deng, Xiaoyang Liu, Ge Gao, Xianbao Sun, Gaolin Liang
Journal: Advanced Healthcare Materials (2022)

Fluorescence Imaging In article number 2200453, Gaolin Liang and co-workers design nearinfrared fluorescence-quenched nanoparticles TK-CBT-NPs for in situ and real-time imaging of ROS activity in Staphylococcus aureus (S. aureus)-infected macrophages and mice. After being endocytosed by S. aureus-infected macrophages, TK-CBT-NPs are disassembled by up-regulated ROS and turn the fluorescence “on”, enabling early and sensitive diagnosis of S. aureus infection.
NIR fluorescence imaging and treatment for cancer immunotherapy
Authors: Homan Kang, Min-Woong Kang, Satoshi Kashiwagi, Hak Soo Choi
Journal: Journal for ImmunoTherapy of Cancer (2022)

Cancer immunotherapy has emerged as one of the most powerful anticancer therapies. However, the details on the interaction between tumors and the immune system are complicated and still poorly understood. Optical fluorescence imaging is a technique that allows for the visualization of fluorescence-labeled immune cells and monitoring of the immune response during immunotherapy. To this end, near-infrared (NIR) light has been adapted for optical fluorescence imaging because it is relatively safe and simple without hazardous ionizing radiation and has relatively deeper tissue penetration into living organisms than visible fluorescence light. In this review, we discuss state-of-the-art NIR optical imaging techniques in cancer immunotherapy to observe the dynamics, efficacy, and responses of the immune components in living organisms. The use of bioimaging labeling techniques will give us an understanding of how the immune system is primed and ultimately developed.
Long‐Acting Protective Ocular Surface by Instilling Adhesive Dual‐Antiviral Nanoparticles (Adv. Healthcare Mater. 14/2022)
Authors: Xinyue Wang, Liangbo Chen, Xinling Wang, Mengmeng Zhang, Fengmin Yang, Feng Wu, Jinyao Liu, Lu Lu, Yan Pang
Journal: Advanced Healthcare Materials (2022)

Ocular Surfaces In article number 2200283, Jinyao Liu, Lu Lu, Yan Pang, and co-workers describe a strategy of forming a long-acting protective ocular surface against external viral invasion by instilling adhesive dual-antiviral nanoparticles, which are enabled by coating antiviral agent-loaded nanoparticles with a “double-lock” hybrid cell membrane.
Flexible 3D Nanonetworked Silica Film as a Polymer‐Free Drug‐Eluting Stent Platform to Effectively Suppress Tissue Hyperplasia in Rat Esophagus (Adv. Healthcare Mater. 14/2022)
Authors: Eunyoung Jeon, Jeon Min Kang, Ga‐Hyun Bae, Chu Hui Zeng, Seungyong Shin, Byeongdu Lee, Wooram Park, Jung‐Hoon Park, Joonseok Lee
Journal: Advanced Healthcare Materials (2022)

Nanonetworked Films In article number 2200389 by Wooram Park, Jung-Hoon Park, Joonseok Lee, and co-workers, a large scale 3D nanonetworked silica film (NSF) is constructed on an entire metallic stent surface to function as a drug delivery platform, which shows excellent mechanical stability, flexibility, and adhesion. The NSF with an antiproliferative agent allows in vivo drastic suppression of stentinduced tissue hyperplasia and restenosis.
Iron effects versus metabolic alterations in hereditary hemochromatosis driven bone loss
Authors: Ulrike Baschant, Sandro Altamura, Peter Steele-Perkins, Martina U. Muckenthaler, Maja Vujić Spasić, Lorenz C. Hofbauer, Andrea U. Steinbicker, Martina Rauner
Journal: Trends in Endocrinology and Metabolism (2022)
Polymer Composite Sponges with Inherent Antibacterial, Hemostatic, Inflammation‐Modulating and Proregenerative Performances for Methicillin‐Resistant <i>Staphylococcus aureus</i>‐Infected Wound Healing
Authors: Wenshuai Liu, Chunfang Yang, Rui Gao, Chao Zhang, Wenbin Ou‐Yang, Zujian Feng, Chuangnian Zhang, Xiangbin Pan, Pingsheng Huang, Deling Kong, Weiwei Wang
Journal: Advanced Healthcare Materials (2022)

Adv. Healthcare Mater. 2021, 10, 2101247 https://doi.org/10.1002/adhm.202101247 In the original version of this article, the fluorescence photo for PQC sponge-treated MRSA (Figure 3C, third row) was incorrect. The original image was from the time point of 0.5 h, while the representative image obtained at 1 h post treatment should be displayed. The corrected Figure 3C is provided here. Results and conclusions of this paper are not affected by this mistake. The authors apologize for any inconvenience or confusion caused.
Not so spontaneous: Multi-dimensional representations of behaviors and context in sensory areas
Authors: Lilach Avitan, Carsen Stringer
Journal: Neuron (2022)

Sensory areas are spontaneously active in the absence of sensory stimuli. This spontaneous activity has long been studied; however, its functional role remains largely unknown. Recent advances in technology, allowing large-scale neural recordings in the awake and behaving animal, have transformed our understanding of spontaneous activity. Studies using these recordings have discovered high-dimensional spontaneous activity patterns, correlation between spontaneous activity and behavior, and dissimilarity between spontaneous and sensory-driven activity patterns. These findings are supported by evidence from developing animals, where a transition toward these characteristics is observed as the circuit matures, as well as by evidence from mature animals across species. These newly revealed characteristics call for the formulation of a new role for spontaneous activity in neural sensory computation.
ELK3 modulates the antitumor efficacy of natural killer cells against triple negative breast cancer by regulating mitochondrial dynamics
Authors: Joo Dong Park, Kwang-Soo Kim, Seung Hee Choi, Gae Hoon Jo, Jin-Ho Choi, Si-Won Park, Eun-Su Ko, Minwook Lee, Dae-Keum Lee, Hye Jung Jang, Sohyun Hwang, Hae-Yun Jung, Kyung-Soon Park
Journal: Journal for ImmunoTherapy of Cancer (2022)

Triple negative breast cancer (TNBC) is the most lethal subtype of breast cancer due to its aggressive behavior and frequent development of resistance to chemotherapy. Although natural killer (NK) cell-based immunotherapy is a promising strategy for overcoming barriers to cancer treatment, the therapeutic efficacy of NK cells against TNBC is below expectations. E26 transformation-specific transcription factor ELK3 (ELK3) is highly expressed in TNBCs and functions as a master regulator of the epithelial-mesenchymal transition.Two representative human TNBC cell lines, MDA-MB231 and Hs578T, were exposed to ELK3-targeting shRNA or an ELK3-expressing plasmid to modulate ELK3 expression. The downstream target genes of ELK3 were identified using a combined approach comprising gene expression profiling and molecular analysis. The role of ELK3 in determining the immunosensitivity of TNBC to NK cells was investigated in terms of mitochondrial fission-fusion transition and reactive oxygen species concentration both in vitro and in vivo.ELK3-dependent mitochondrial fission-fusion status was linked to the mitochondrial superoxide concentration in TNBCs and was a main determinant of NK cell-mediated immune responses. We identified mitochondrial dynamics proteins of 51 (Mid51), a major mediator of mitochondrial fission, as a direct downstream target of ELK3 in TNBCs. Also, we demonstrated that expression of ELK3 correlated inversely with that of Mid51, and that the ELK3-Mid51 axis is associated directly with the status of mitochondrial dynamics. METABRIC analysis revealed that the ELK3-Mid51 axis has a direct effect on the immune score and survival of patients with TNBC.Taken together, the data suggest that NK cell responses to TNBC are linked directly to ELK3 expression levels, shedding new light on strategies to improve the efficacy of NK cell-based immunotherapy of TNBC.
Microglia-derived PDGFB promotes neuronal potassium currents to suppress basal sympathetic tonicity and limit hypertension
Authors: Qianqian Bi, Chao Wang, Guo Cheng, Ningting Chen, Bo Wei, Xiaoli Liu, Li Li, Cheng Lu, Jian He, Yuancheng Weng, Chunyou Yin, Yunfan Lin, Shu Wan, Li Zhao, Jiaxi Xu, Yi Wang, Yan Gu, Xiao Z. Shen, Peng Shi
Journal: Immunity (2022)
Colocalized targeting of TGF-β and PD-L1 by bintrafusp alfa elicits distinct antitumor responses
Authors: Yan Lan, Tsz-Lun Yeung, Hui Huang, Ansgar A Wegener, Somdutta Saha, Mira Toister-Achituv, Molly H Jenkins, Li-Ya Chiu, Adam Lazorchak, Ohad Tarcic, Hong Wang, Jin Qi, George Locke, Doron Kalimi, Guozhong Qin, Bo Marelli, Huakui Yu, Alec W Gross, Melissa G Derner, Maria Soloviev, Mathieu Botte, Aroop Sircar, Hong Ma, Vanita D Sood, Dong Zhang, Feng Jiang, Kin-Ming Lo
Journal: Journal for ImmunoTherapy of Cancer (2022)

Bintrafusp alfa (BA) is a bifunctional fusion protein designed for colocalized, simultaneous inhibition of two immunosuppressive pathways, transforming growth factor-β (TGF-β) and programmed death-ligand 1 (PD-L1), within the tumor microenvironment (TME). We hypothesized that targeting PD-L1 to the tumor by BA colocalizes the TGF-β trap (TGF-βRII) to the TME, enabling it to sequester TGF-β in the tumor more effectively than systemic TGF-β blockade, thereby enhancing antitumor activity.Multiple technologies were used to characterize the TGF-β trap binding avidity. BA versus combinations of anti-PD-L1 and TGF-β trap or the pan-TGF-β antibody fresolimumab were compared in proliferation and two-way mixed lymphocyte reaction assays. Immunophenotyping of tumor-infiltrating lymphocytes (TILs) and RNA sequencing (RNAseq) analysis assessing stromal and immune landscape following BA or the combination therapy were performed in MC38 tumors. TGF-β and PD-L1 co-expression and their associated gene signatures in MC38 tumors and human lung carcinoma tissue were studied with single-cell RNAseq (scRNAseq) and immunostaining. BA-induced internalization, degradation, and depletion of TGF-β were investigated in vitro.BA and fresolimumab had comparable intrinsic binding to TGF-β1, but there was an ~80× avidity-based increase in binding affinity with BA. BA inhibited cell proliferation in TGF-β-dependent and PD-L1-expressing cells more potently than TGF-β trap or fresolimumab. Compared with the combination of anti-PD-L1 and TGF-β trap or fresolimumab, BA enhanced T cell activation in vitro and increased TILs in MC38 tumors, which correlated with efficacy. BA induced distinct gene expression in the TME compared with the combination therapy, including upregulation of immune-related gene signatures and reduced activities in TGF-β-regulated pathways, such as epithelial-mesenchymal transition, extracellular matrix deposition, and fibrosis. Regulatory T cells, macrophages, immune cells of myeloid lineage, and fibroblasts were key PD-L1/TGF-β1 co-expressing cells in the TME. scRNAseq analysis suggested BA modulation of the macrophage phenotype, which was confirmed by histological assessment. PD-L1/TGF-β1 co-expression was also seen in human tumors. Finally, BA induced TGF-β1 internalization and degradation in the lysosomes.BA more effectively blocks TGF-β by targeting TGF-β trap to the tumor via PD-L1 binding. Such colocalized targeting elicits distinct and superior antitumor responses relative to single agent combination therapy.
A RET::GRB2 fusion in pheochromocytoma defies the classic paradigm of RET oncogenic fusions
Authors: Cynthia M. Estrada-Zuniga, Zi-Ming Cheng, Purushoth Ethiraj, Qianjin Guo, Hector Gonzalez-Cantú, Elaina Adderley, Hector Lopez, Bethany N. Landry, Abir Zainal, Neil Aronin, Yanli Ding, Xiaojing Wang, Ricardo C.T. Aguiar, Patricia L.M. Dahia
Journal: Cell Reports Medicine (2022)

The RET kinase receptor is a target of mutations in neural crest tumors, including pheochromocytomas, and of oncogenic fusions in epithelial cancers. We report a RET::GRB2 fusion in a pheochromocytoma in which RET, functioning as the upstream partner, retains its kinase domain but loses critical C-terminal motifs and is fused to GRB2, a physiological RET interacting protein. RET::GRB2 is an oncogenic driver that leads to constitutive, ligand-independent RET signaling; has transforming capability dependent on RET catalytic function; and is sensitive to RET inhibitors. These observations highlight a new driver event in pheochromocytomas potentially amenable for RET-driven therapy.
Persistence of MERS-CoV-spike-specific B cells and antibodies after late third immunization with the MVA-MERS-S vaccine
Authors: Leonie M. Weskamm, Anahita Fathi, Matthijs P. Raadsen, Anna Z. Mykytyn, Till Koch, Michael Spohn, Monika Friedrich, Etienne Bartels, Swantje Gundlach, Thomas Hesterkamp, Verena Krähling, Susan Lassen, My Linh Ly, Joseph H. Pötsch, Stefan Schmiedel, Asisa Volz, Madeleine E. Zinser, Bart L. Haagmans, Stephan Becker, Gerd Sutter, Christine Dahlke, Marylyn M. Addo
Journal: Cell Reports Medicine (2022)

The Middle East respiratory syndrome (MERS) is a respiratory disease caused by MERS coronavirus (MERS-CoV). In follow up to a phase 1 trial, we perform a longitudinal analysis of immune responses following immunization with the modified vaccinia virus Ankara (MVA)-based vaccine MVA-MERS-S encoding the MERS-CoV-spike protein. Three homologous immunizations were administered on days 0 and 28 with a late booster vaccination at 12 ± 4 months. Antibody isotypes, subclasses, and neutralization capacity as well as T and B cell responses were monitored over a period of 3 years using standard and bead-based enzyme-linked immunosorbent assay (ELISA), 50% plaque-reduction neutralization test (PRNT50), enzyme-linked immunospot (ELISpot), and flow cytometry. The late booster immunization significantly increases the frequency and persistence of spike-specific B cells, binding immunoglobulin G1 (IgG1) and neutralizing antibodies but not T cell responses. Our data highlight the potential of a late boost to enhance long-term antibody and B cell immunity against MERS-CoV. Our findings on the MVA-MERS-S vaccine may be of relevance for coronavirus 2019 (COVID-19) vaccination strategies.
Effect of tocilizumab, sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: a systematic review and meta-analysis
Authors: Arthur M. Albuquerque, Igor Eckert, Lucas Tramujas, Guillaume Butler-Laporte, Emily G. McDonald, James M. Brophy, Todd C. Lee
Journal: Clinical Microbiology and Infection (2022)
Manipulation of the inflammatory reflex as a therapeutic strategy
Authors: Mark J. Kelly, Caitríona Breathnach, Kevin J. Tracey, Seamas C. Donnelly
Journal: Cell Reports Medicine (2022)

The cholinergic anti-inflammatory pathway is the efferent arm of the inflammatory reflex, a neural circuit through which the CNS can modulate peripheral immune responses. Signals communicated via the vagus and splenic nerves use acetylcholine, produced by Choline acetyltransferase (ChAT)+ T cells, to downregulate the inflammatory actions of macrophages expressing α7 nicotinic receptors. Pre-clinical studies using transgenic animals, cholinergic agonists, vagotomy, and vagus nerve stimulation have demonstrated this pathway's role and therapeutic potential in numerous inflammatory diseases. In this review, we summarize what is understood about the inflammatory reflex. We also demonstrate how pre-clinical findings are being translated into promising clinical trials, and we draw particular attention to innovative bioelectronic methods of harnessing the cholinergic anti-inflammatory pathway for clinical use.
Long-term 2-year safety and efficacy of tralokinumab in adults with moderate-to-severe atopic dermatitis: Interim analysis of the ECZTEND open-label extension trial
Authors: Andrew Blauvelt, Richard G. Langley, Jean-Philippe Lacour, Darryl Toth, Vivian Laquer, Stefan Beissert, Andreas Wollenberg, Pedro Herranz, Andrew E. Pink, Ketty Peris, Stine Fangel, Le Gjerum, Joshua Corriveau, Hidehisa Saeki, Richard B. Warren, Eric Simpson, Kristian Reich
Journal: Journal of the American Academy of Dermatology (2022)

Additional long-term treatments are needed for moderate-to-severe atopic dermatitis (AD). An ongoing, open-label, 5-year extension trial, ECZTEND (NCT03587805), assesses tralokinumab plus optional topical corticosteroids in participants from previous tralokinumab parent trials (PTs) with moderate-to-severe AD.To evaluate the safety and efficacy of up to 2 years tralokinumab treatment in a post hoc interim analysis.Safety analyses included adults from completed PTs enrolled in ECZTEND, regardless of tralokinumab exposure duration. Efficacy analyses included adult participants treated with tralokinumab in ECZTEND for ≥1 year and subgroup analyses of those on tralokinumab for 2 years (1 year from PT, 1 year in ECZTEND). Primary end point was the number of adverse events with additional efficacy end points.Participants on tralokinumab had an exposure-adjusted rate of 237.8 adverse events/100 patient-years' exposure (N = 1174) in the safety analysis set. Exposure-adjusted incidence rates of common adverse events were comparable to PTs, although at lower rates. With 2 years of tralokinumab, improvements in extent and severity of AD were sustained, with Eczema Area and Severity Index (EASI-75) in 82.5% of participants (N = 345).Possible selection bias; no placebo arm; some participants experienced treatment gaps between PTs and ECZTEND.Over 2 years, tralokinumab was well tolerated and maintained long-term control of AD signs and symptoms.
COVID-19 morbidity decreases with tixagevimab–cilgavimab preexposure prophylaxis in kidney transplant recipient nonresponders or low-vaccine responders
Authors: Hannah Kaminski, Mickael Gigan, Agathe Vermorel, Manon Charrier, Laura Guirle, Frederic Jambon, Arthur Lacapère, Coline Ménard, Karine Moreau, Martine Neau-Cransac, Marine Novion, Frederique Pribat, Benjamin Taton, Sébastien Borde, Laure Burguet, Charlie Martinez, Magali Jasiek, Pauline D’Halluin, Marie-Edith Lafon, Pierre Merville, Lionel Couzi
Journal: Kidney International (2022)